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A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs.

Schul, Wouter and Liu, Wei and Xu, Hao Ying and Flamand, Marie and Vasudevan, Subhash (2007) A dengue fever viremia model in mice shows reduction in viral replication and suppression of the inflammatory response after treatment with antiviral drugs. The Journal of Infectious Diseases, 195 (5). pp. 665-674. ISSN 0022-1899

Abstract

Dengue fever is an emerging arboviral disease for which no vaccine or antiviral treatment exists and that causes thousands of fatalities each year. To develop an in vivo test system for antidengue drugs, AG129 mice, which are deficient for the interferon- alpha / beta and - gamma receptors, were injected with unadapted dengue virus, resulting in a dose-dependent transient viremia lasting several days and peaking on day 3 after infection. Additionally, nonstructural protein 1, increased levels of proinflammatory cytokines, and neutralizing IgM and IgG antibodies were found, and mice had splenomegaly. Oral administration of the antiviral compounds 7-deaza-2'-C-methyl-adenosine, N-nonyl-deoxynojirimycin, or 6-O-butanoyl castanospermine significantly reduced viremia in a dose-dependent manner, even after delayed treatment, leading to a reduction of splenomegaly and proinflammatory cytokine levels. The results validate this dengue viremia mouse model as a suitable system for testing antidengue drugs and indicate that antiviral treatment during the acute phase of dengue fever can reduce the severity of the disease.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Embargo of 12 months to 3 years for use in institutional repository; Authors are encouraged to use publisher version (PDF) or link to publisher version
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Date Deposited: 14 Dec 2009 14:01
Last Modified: 31 Jan 2013 01:20
URI: https://oak.novartis.com/id/eprint/306

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